Zander Smith showed up in Port Charles in the summer of 2000. Initially, he was a small time drug dealer, selling at parties for mob boss Joseph Sorel. When Zander was framed for the murder of undercover cop Ted Wilson, he panicked and took Emily Quartermaine hostage. Zander and Emily became friends while hiding from the cops. Eventually Zander was arrested, but Emily fought to get him released.

With the help of attorney Alexis Davis and Sorel's rival mob boss Sonny Corinthos, Zander was released on Christmas Eve. His joy was short lived when he, Emily, Alexis and Sonny were ambushed by Sorel's men in front of the police station. Zander and Sonny were both shot, but surived. Against all odds, Zander and Emily fell in love. She transformed him into someone he never thought he could be...someone worthy.

The Quartermaines were desperate to keep Zander and Emily apart, fearing for Emily's safety. When the two young lovers left town after receiving a death threat from Sorel, their bus was hit by a train. Emily was paralyzed. While in the hospital, another of Sorel's men came after them, but was fought off by Zander and Emily's cousin, Ned Ashton. Zander insisted that she be sent away to rehab for protection.

Despite Emily's fear that something bad would happen if they were separated, Zander convinced her to leave, promising to join her once Sorel was captured. Sadly, Zander and Emily never reunited. After Sorel was captured (and eventually murdered), Zander took a job assignment from Sonny that destroyed everything. He coerced Emily's brother AJ into signing away his parental rights to son Michael, so Sonny could adopt him. Emily broke up with Zander over the phone.

Zander threw himself into his work. He took on a new assignment: Befriend Sonny's ex-wife Carly and keep her out of trouble. Zander and Carly turned out to be kindred spirits and became best friends. Unfortunately she tried to seduce him as a way to get back at Sonny and a pride-wounded Zander kicked her out. When Carly was presumed dead in a car accident, Zander blamed himself and told Sonny about the incident.

Carly "returned from the dead" and got back together with Sonny, hurting Zander who'd been falling in love with her. Sonny's ex-right hand man, Jason Morgan, came back to town and Zander was fired. Seeking revenge, Zander sold information to one of Sonny's rivals. Jason caught him in the act and gave Zander a beating as a warning. Emily's best friend Elizabeth came to Zander's rescue.